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<p>The efficacy of in situ cancer vaccination has been hampered by a poor spatiotemporal orchestration of multiple key steps of the cancer-immunity cycle in most tumours and systemic toxicity related to therapeutic strategies. Here we report a systemic injectable and pyroptosis-enabled nanoadjuvant that evokes the secretion of a vaccine-like pyroptosome in the tumour area for robust antitumour immunity. This systemic injectable and pyroptosis-enabled nanoadjuvant induces vigorous immunogenic pyroptosis, triggering the efficient release of tumour antigen-rich pyroptosomes, damage-associated molecular patterns and proinflammatory cytokines. Photoactivatable release of a TLR7/8 agonist into the pyroptosome generates an in situ cancer vaccine platform that cooperatively activates the cancer-immunity cycle and avoids systemic toxicity. The vaccine boosts both innate and adaptive immune responses, facilitating the eradication of primary tumours and metastatic nodules, thereby providing long-lasting cancer prevention. Overall, the rational design of pyroptosis-inducing nanomedicines for boosting the cancer-immunity cycle reported here might aid in the development of more efficient personalized cancer immunotherapy approaches.</p>

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In situ-generated vaccine-like pyroptosome for personalized cancer immunotherapy

  • 期刊论文

  • 发表日期：

    2026年3月3日

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  • Binlong Chen,
  • Fangjie Wan,
  • Heming Xia,
  • Xingquan Pan,
  • Letong Wang,
  • Yaoqi Wang,
  • Yue Yan,
  • Jianxiong Liu,
  • Mingmei Tang,
  • Ye Yang,
  • Mengmeng Qin,
  • Jiaona Ren,
  • Bushu Zhou,
  • Lijun Zhong,
  • Wei Chen,
  • Chuanhui Han,
  • Mi Deng,
  • Qiang Zhang,
  • Yiguang Wang

摘要

The efficacy of in situ cancer vaccination has been hampered by a poor spatiotemporal orchestration of multiple key steps of the cancer-immunity cycle in most tumours and systemic toxicity related to therapeutic strategies. Here we report a systemic injectable and pyroptosis-enabled nanoadjuvant that evokes the secretion of a vaccine-like pyroptosome in the tumour area for robust antitumour immunity. This systemic injectable and pyroptosis-enabled nanoadjuvant induces vigorous immunogenic pyroptosis, triggering the efficient release of tumour antigen-rich pyroptosomes, damage-associated molecular patterns and proinflammatory cytokines. Photoactivatable release of a TLR7/8 agonist into the pyroptosome generates an in situ cancer vaccine platform that cooperatively activates the cancer-immunity cycle and avoids systemic toxicity. The vaccine boosts both innate and adaptive immune responses, facilitating the eradication of primary tumours and metastatic nodules, thereby providing long-lasting cancer prevention. Overall, the rational design of pyroptosis-inducing nanomedicines for boosting the cancer-immunity cycle reported here might aid in the development of more efficient personalized cancer immunotherapy approaches.